Genetic Links for IBD

Study uncovers new genetic links for inflammatory bowel disease

Researchers of Crohn's disease and ulcerative colitis, sharing raw data and newly collected genetic information from centers around the world, have found associations suggesting a fundamental connection between risk of inflammatory bowel disease (IBD) and genes involved in immune-related diseases and the immune system's response to pathogens.

The study, published in the Nov. 1 edition of Nature, brings together data from 75,000 inflammatory bowel disease patients and controls and marks an important step toward honing in on why these illnesses occur and personalizing treatments for them. The study also identified 71 new genes associated with IBD, many of which are shared with other autoimmune conditions such as psoriasis, diabetes and ankylosing spondylitis.

"This is a real pathway to personalized medicine," said Dermot McGovern, MD, PhD, director of translational medicine at Cedars-Sinai's F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and a senior study author. "The findings from this study reveal a significant amount about the underlying biology of what's causing these conditions. IBD is most likely a collection of different conditions, and if we can define them by their molecular causes, we will then be able to tailor treatment approaches that are more appropriate to individual patients."

Inflammatory bowel disease, treated at Cedars-Sinai's Inflammatory Bowel Disease Center, affects about 2 million children and adults in the United States. Crohn's disease and ulcerative colitis cause debilitating symptoms, such as stomach pain, diarrhea, fatigue, intestinal bleeding and weight loss. There is no known cure at this time.

The study brought together researchers and data from an international IBD genetics consortium, which includes Cedars-Sinai Medical Center, the Broad Institute, Massachusetts General Hospital, Yale School of Medicine and dozens of other institutions. "If we want to get more hits but also dissect the differences between Crohn's disease and ulcerative colitis or understand the commonalities, we really need to share all of our genetic data," said co-first author Stephan Ripke, a researcher at the Broad Institute and Massachusetts General Hospital.

The new study identified 71 additional genetic associations for IBD, bringing the total number of identified genes associated with the disease to more than160 – significantly more genes than have been identified for any other complex genetic condition. In addition to uncovering the link between IBD and other immune disorders through these genes, the new research also suggests overlap between IBD susceptibility genes and genes tied to the immune system's response to mycobacterial infections, including tuberculosis and leprosy. This suggests that the ability of humans to resist these infections over many thousands of years may have resulted in the presence of these genetic variants that increase the risk of IBD.

Besides drawing on original data from previous studies, the work utilized a relatively new genotyping tool known as the immunochip, which "tests" about 200,000 sites in the genome previously tied to autoimmune and inflammatory diseases.

Cedars-Sinai data used in this study did not include patient identities or other personal information.